Transcriptomic changes triggered by ouabain in rat cerebellum granule cells: Role of α3- and α1-Na+,K+-ATPase-mediated signaling

Autoři: Larisa V. Smolyaninova aff001;  Alexandra A. Shiyan aff001;  Leonid V. Kapilevich aff002;  Alexander V. Lopachev aff003;  Tatiana N. Fedorova aff003;  Tatiana S. Klementieva aff004;  Aleksey A. Moskovtsev aff004;  Aslan A. Kubatiev aff004;  Sergei N. Orlov aff001
Působiště autorů: Department of Biomembranes, Faculty of Biology, M. V. Lomonosov Moscow State University, Moscow, Russia aff001;  Department of Sports Tourism Sports Physiology and Medicine, National Research Tomsk State University, Tomsk, Russia aff002;  Laboratory of Clinical and Experimental Neurochemistry, Research Center of Neurology, Moscow, Russia aff003;  Department of Molecular and Cell Pathophysiology, Institute of General Pathology and Pathophysiology, Moscow, Russia aff004;  Central Research Laboratory, Siberian Medical State University, Tomsk, Russia aff005
Vyšlo v časopise: PLoS ONE 14(9)
Kategorie: Research Article
doi: 10.1371/journal.pone.0222767


It was shown previously that inhibition of the ubiquitous α1 isoform of Na+,K+-ATPase by ouabain sharply affects gene expression profile via elevation of intracellular [Na+]i/[K+]i ratio. Unlike other cells, neurons are abundant in the α3 isoform of Na+,K+-ATPase, whose affinity in rodents to ouabain is 104-fold higher compared to the α1 isoform. With these sharp differences in mind, we compared transcriptomic changes in rat cerebellum granule cells triggered by inhibition of α1- and α3-Na+,K+-ATPase isoforms. Inhibition of α1- and α3-Na+,K+-ATPase isoforms by 1 mM ouabain resulted in dissipation of transmembrane Na+ and K+ gradients and differential expression of 994 transcripts, whereas selective inhibition of α3-Na+,K+-ATPase isoform by 100 nM ouabain affected expression of 144 transcripts without any impact on the [Na+]i/[K+]i ratio. The list of genes whose expression was affected by 1 mM ouabain by more than 2-fold was abundant in intermediates of intracellular signaling and transcription regulators, including augmented content of Npas4, Fos, Junb, Atf3, and Klf4 mRNAs, whose upregulated expression was demonstrated in neurons subjected to electrical and glutamatergic stimulation. The role [Na+]i/[K+]i-mediated signaling in transcriptomic changes involved in memory formation and storage should be examined further.

Klíčová slova:

DNA-binding proteins – Gene expression – MTT assay – Neurons – Transcriptome analysis – Cerebellum – Olfactory receptors – Granule cells


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